Cardio-KIN 232

b. Endothelin c. ADH e. Epinephrine g. Angiotensin II h. Norepinephrine (o Humoral Factors: VASOCONSTRICTORS 1. NOREPINEHPRINE (direct) and EPINEPHRINE (indirect) 2. ANGIOTENSIN II 3. ADH (VASOPRESSIN) (released in high amounts during hemorrhage where it can increase arterial pressure by 60 mmHg alone) 4. ENDOTHELIN (Extremely powerful in response to severe tissue trauma to prevent extensive bleeding.) ----------------------------------------------- o Humoral Factors: VASODILATORS 1. BRADYKININ (Inflamed tissues release bradykinin which lead to powerful arteriolar vasodilation and increased capillary permeability) 2. HISTAMINE (released by virtually all tissues by mast cells of damaged tissues or basophils in the blood; especially prominent during allergic reactions)

11. Select all of the humoral factors VASOCONSTRICTORS a. Histamine b. Endothelin c. ADH d. Bradykinin e. Epinephrine f. Oxytocin g. Angiotensin II h. Norepinephrine

exercise induced hypoxia

40% of elite endurance athletes have such high cardiac outputs that they see a drop in blood oxygen levels at high intensities (limiting their performance)-->this is due to a short red blood cell transit time through the LUNG (pulmonary) capillaries. -Ultimately this is the limit to their performance and these athletes can NEVER exceed this ability. -RBC travels too quickly past lungs to pick up sufficient oxygen (muscle can adapt but lungs cant completely)

cardiac cycle

A complete heartbeat consisting of contraction and relaxation of both atria and both ventricles The _______________is essentially split into two phases, systole (the contraction phase) and diastole (the relaxation phase). Each of these is then further divided into an atrial and ventricular component. The _____________________________ therefore proceeds in four stages: 1.Atrial systole: lasts about 0.1 seconds - both atria contract and force the blood from the atria into the ventricles. 2.Ventricular systole: lasts about 0.3 seconds - both ventricles contract, blood is forced to the lungs via the pulmonary trunk, and the rest of the body via the aorta. 3.Atrial diastole: lasting about 0.7 seconds - relaxation of the atria, during which the atria fill with blood from the large veins (the vena cavae). 4.Ventricular diastole: lasts about 0.5 seconds - begins before atrial systole, allowing the ventricles to fill passively with blood from the atria.

1600 (Posillues' Law: resistance through blood vessel is proportional to the pressure difference on both ends of tubes--thus resistance is INVERSELY proportional to radius to the 4th power -dilating a vessel to 2x the size= reduce resistant by 1600% -arterial vessels constrict and dilate so blood flow and pressure are greatly influenced)

A two-fold increase in the radius of a blood vessel lumen would cause a _____% increase in blood vessel resistance (Posillues Law).

stiff arterial vessels (--> lack of arterial compliance o Large difference between systolic and diastolic is dangerous; linked to organ damage)

Above average pulse pressure (60 mmHg) suggests ....

collateral circulation

Additional blood vessels are grown as an alternate circulation path around a blocked artery or vein via another path, such as nearby minor vessels. - almost all humans over 60 have at least one small coronary vessel occluded but unnoticed because of rapid growth of collateral vessels which avoid myocardial damage

45 (• RHR (Resting Heart Rate): the number of heart beats per minute while you're at rest • Stroke volume = cardiac output divided by heart rate 110 mL = 4900/x X= 44.5 mL --> 45 mL o Cardiac output: Heart Rate x stroke volume • Normal resting CO = 4900 mL/5 L per minute Stroke volume: amount of blood that comes out of every heart beat Heart rate: number of heart beats per minute)8. The second heart sound. a. Closure of the AV valves (Mitral and Tricuspid). b. Closure of the Aortic and Pulmonary Valves.

An athlete with a stroke volume of 110 mL would be expected to have a RHR of around ______ mL.

c. Vagal (• Vagal Tone: Activity of the vagus nerve that lowers the heart rate and decreases blood pressure (elevating levels of rest and digest activity); Increase potassium permeability - decrease resting potential; athletes haver higher vagal tone o Exercise-induced bradycardia: endurance athletes have higher vagal tone and sinus bradycardia (usually a sign of fitness and nothing serious))

An athlete's heart would usually possess greater _______ tone which would slow the heart rate and allow for longer filling time. a. Adrenergic b. Sympathetic c. Vagal d. None of these

c. 100 mL (• Stroke volume = cardiac output divided by heart rate = 4900/49 = 100 mL o Cardiac output: Heart Rate x stroke volume • Normal resting CO = 4900 mL/5 L per minute Stroke volume: amount of blood that comes out of every heart beat Heart rate: number of heart beats per minute o Athletes have a LARGER stroke volume and GREATER volume of O2 is delivered to the body per heartbeat; larger ventricle-->stronger contraction to eject more blood)

An endurance athlete has a resting heart rate of 49 bpm, what is the predicted stroke volume? a. 50 mL b. 80 mL c. 100 mL d. 120 mL

VEFG, fibroblast, growth factor, angiogenin

Angiogenic Factors

reactive hyperemia

(part of ACUTE CONTROL of the oxygen -lack theory) occluded blood flow increases 4-7 fold when opened long enough to "pay back" the exact O2 deficit during occlusion (metabolic blood flow regulation)--> lack of oxygen causes an immediate payback of blood flow (think of rubber band around finger) occlusion--> removal-->dramatic increase in blood flow

active hyperemia

(part of ACUTE CONTROL of the oxygen -lack theory) up to 20 fold increase during muscle contraction (EXERCISE) releasing large quantities of vasodilator substances-->metabolically active muscle tissues cause blood vessels to dilate o Arteries over-dilate during exercise -> constrict as a response (burning sensation) -> less oxygen to muscles results in switch anaerobic metabolism -> production of lactate

ST segment

(part of EKG) beginning of ventricular repolarization, should be flat (very sensitive to oxygen levels in heart and if elevated, sign of someone having a heart attack)

PR interval

(part of EKG) AV delay to allow ventricular chambers to fill up w/ blood; follow atrial depolarization to ventricular contraction. signal enters ventricle via AV node

QRS wave

(part of EKG) ventricular depolarization (triggers main pumping contractions)

T wave

(part of EKG) ventricular repolarization (potassium comes back out of heart through cell membranes), heart ventricles are relaxing

P wave

(part of EKG) Atrial depolarization in response to SA node triggering (sodium has gone in followed by calcium and pumps blood to ventricles)

Thoracic Pump

(type of venous capacitance) every time you take a breath in, that breath in expands your blood vessels; creates changes in thoracic pressure to draw blood up through heart like straw o Veins have one-way valve _____: Breathing--> changes to blood vessels, venous return to heart

Muscle Pump

(type of venous capacitance) muscles contracting from a little movement massages veins to squeeze blood up back to the heart (one-way valves to prevent blood from seeping back down) Varicose Veins: veins with damaged valves Staying still after exercise -> poor venous return o __________: Move around--> muscle contract, veins squeeze

a. visceral organs b. working muscles

**In general, higher intensity takes blood flow from ____a_____ and send blood to ___b____.

a. Higher contractility due to the Treppe Effect. (• Treppe Effect: the graduated series of increasingly vigorous contractions that results when a corresponding series of identical stimuli is applied to a rested muscle. — called also staircase effect, staircase phenomenon. o At a higher heart rate, greater amount contractility ---a chronotropic effect (heart beats FASTER) naturally causes inotropic affect (hear beats STRONGER))

Increased heart rate leads to a. Higher contractility due to the Treppe Effect. b. Less contractility due to less EDV.

b. Nitric oxide (EDRF) (• Endothelium-Derived Relaxing Factor (EDRF): is produced and released by the endothelium to promote smooth muscle relaxation in response to rapid blood flow (viscous drag and shear stress along endothelial walls) • Endothelial Nitric Oxide Synthase: - blood flow causes stress on blood vessel walls, causing endothelial cells to activate the enzyme EDRF. - EDRF produces nitric oxide, which comes out of the lining of the artery and diffuses into the media area where it elevates cyclic GMP (second messenger). - This inhibits calcium release and leads to the relaxation of cells; cells dilate and arteries expand. Cascade of events attenuates sympathetic vasoconstriction and induces arterial smooth muscle relaxation to increase blood flow • Exercise increases the expression of nitric oxide synthase)

Increased shear stress along a blood vessel wall increases the release of _________ from the endothelial cells which causes SMC relaxation. a. Potassium b. Nitric oxide (EDRF) c. Superoxide d. Calcium

Beri Beri

Inflammation of nerves, heart failure and weakening of capillary walls due to a lack of B (B1-thiamin) vitamins and Niacin and Riboflavin lead to 2-3 fold increase in blood flow) -These B vitamins are required for energy/oxidative phosphorylation (smooth muscle cells of arteries cannot constrict/dilate) -lack of nutrients --> inability of smooth muscles to contract and induce venous return --> cannot get blood to brain standing up (b/c blood stays pooled in legs), cannot redirect oxygen/nutrients to muscles --> dizzy, immobile o explains oxygen lack-theory

stopcocks/ resistance vessels

Arterial vessels --> __________ of the circulation; conserve blood flow (ex: when cold, take blood away from extremities and pool towards organs, causing vasoconstriction)

Mean Arterial Pressure (MAP)

Average arterial pressure during one cardiac cycle (Considered a better indicator of perfusion to vital organs than systolic blood pressure) oMAP = (2 x (DBP) + SBP) / 3 (2x more time spent in diastole than systole + systolic Blood pressure) divided by 3 • 2/3 time in diastole and 1/3 in systole • Ex: BP 120/80 = (120+160)/3 = 93 MAP o 60 mmHG of arterial pressure is required for perfusion of the brain to sustain blood flow to main arterial organs (anything lower can result in shock)

vasodilator (Inflamed tissues release bradykinin which lead to powerful arteriolar vasodilation and increased capillary permeability HISTAMINE (released by virtually all tissues by mast cells of damaged tissues or basophils in the blood; especially prominent during allergic reactions)

BRADYKININ and Histamines; vasoconstrictors or vasodilators?

c. 1600% (• Posillues' Law: resistance through blood vessel is proportional to the pressure difference on both ends of tubes - thus the resistance is inversely proportional to radius to the fourth power o Dilating a vessel to 2x the size = reduce resistance by 1600% o Arterial vessels constrict and dilate so blood flow and pressure are greatly influenced)

Based on the Poiseuille's Law, if the diameter of an arterial vessel's lumen constricts to half the size, resistance to flow will increase by ________. a. 80% b. 400% c. 1600% d. 60%

Endothelium-Derived Relaxing Factor (EDRF) is produces and released by the endothelium to promote smooth muscle relaxation in response to rapid blood flow (vicious drag and shear stress along endothelium walls) • Endothelial Nitric Oxide Synthase: o blood flow causes stress on blood vessel walls, causing endothelial cells to activate the enzyme EDRF. o EDRF produces nitric oxide, which comes out of the lining of the artery and diffuses into the media area where it elevates cyclic GMP (second messenger). o This inhibits calcium release and leads to the relaxation of cells; cells dilate and arteries expand. Cascade of events attenuates sympathetic vasoconstriction and induces arterial smooth muscle relaxation to increase blood flow • Exercise increases the expression of nitric oxide synthase

Be able to describe EDRF.

-Blood flow at REST: LIVER gets majority of blood flow -Blood flow during EXERCISE: MUSCLES recieve most blood (; the liver, GI tract, kidney, etc. get less blood) (• **In general, higher intensity takes blood flow from visceral organs and send blood to working muscles)

Be able to describe how blood flow changes from rest to exercise.

a) lower b) higher (o Heart Rate: number of heart beats per minute (heart rate) o stoke volume: how much blood comes out of your heart with every beat)

Being in good shape = ___a___heart beat and __b__ stroke volume

a. True (• CO2 is VASOCONSTRICTOR pulmonary arteries (b/c CO2 is indicator that not enough oxygen being produced) • ***why would a COPD or a smoking patient be susceptible to right side heart failure? o b/c CO2 in lungs causes right side of heart to work that much harder to get vasoconstricted lungs o for smokers, right side of heart always under stress b/c right side of heart is working so hard to get blood flow through vasoconstricted arteries)

CO2 is a vasoconstrictor in the blood vessels of the lungs (pulmonary) CO2 is a vasoconstrictor in pulmonary arteries, but not systemic arteries. a. True b. False

treppe phenomenon

Ca 2+ concentration in the cytosol rises higher and higher with each stimulus causing subsequent twitches to be stronger; Called also staircase phenomenon. As an example, PVCs are very strong contractions because of the _________________________ (more calcium for subsequent contraction). (explains rate-induced contractibility)

veins (the blood vessels that contain most of the blood and that can readily accommodate changes in the blood volume)

Capacitance vessels

heart rate x stroke volume (o Heart Rate: number of heart beats per minute (heart rate) o stoke volume: how much blood comes out of your heart with every beat)

Cardiac Output formula

c. 70 mL (• Stroke Volume (SV): amount of blood that comes out of every heart beat o Normal Resting Stroke Volume = 70 mL o Normal End Diastolic Volume (EDV): volume in average ventricle at end of filling (120 mL) - PRELOAD o Normal End Systolic Volume (ESV): volume of the heart after contraction (50 mL) o Ejection Fraction: 70 mL/120 mL = 59% ; stroke volume (70 mL)/end diastolic volume (120 mL) • If low (around 30%) - indication of heart failure o Preload: filling of the ventricle prior to contraction; preload needs to EXCEED the afterload to have a healthy/adequate stroke volume and ejection fraction to prevent heart failure (EDV) o Afterload: arterial pressure outside ventricle, pressure against which heart works to eject blood)

Common stroke volume in a healthy person at rest a. 50 mL b. 60 mL c. 70 mL d. 80 mL

Pulse Pressure (PP):

Difference between systolic and diastolic pressure o Normal: 40mmHg (b/c normal BP is 115/75 and 115-75=40) o Above average ________(60 mmHg) suggests stiff arterial vessels-->lack of arterial compliance o Large difference between systolic and diastolic is dangerous; linked to organ damage o Which is better 140/80 or 140/90; 140/90 b/c at least arteries are pretty compliant just need to get BP down

a. SA node b. atrial cells c. AV node d. end diastolic volume (EDV) e. Bundle of 'HIS f. Ventricular septum g. purkinje fibers I. Ventricular depolarization

Different steps of conduction pathway through the heart: 1. ___a____ initiates the cardiac action potential (that is why it is called sinus rhythm. Normal 60-80BPM) 2. action potential spreads through ____b____ (via gap functioning containing intercalated disks [nerve fibers connecting cells] to the ___c___ 3. There is a brief AV-delay while the ventricles fill to _____d____ (= ~ 120mL) 4. the _____c____ continues the action potential to the ____e____ 5. then the action potential travels from the ____e____ to RIGHT and LEFT bundle branches of ___f____ 6. then the action potential spreads along the _____g______ to complete ______I_______ (causing contraction)

70 mL/120 mL = 59% (stroke volume (70 mL)/end diastolic volume (120 mL))

Ejection Fraction

Ejection Fraction: stroke volume / end diastolic volume = % (o In normal individual: stroke volume (70 mL) / end diastolic volume (120 mL) = 58%)

Ejection fraction formula

(EDRF = Endothelium-Derived Relaxing Factor) a. nitric oxide b. calcium

Enzyme EDRF produces _____a______ that elevates CYCLIC GMP (second messenger) which INHIBITS ___b____ release and leads to the relaxation of cells; cells dilate and arteries expand

NON-pacemakers

Fast response action potentials--> ventricular cells

MAP = (2 x (DBP) + SBP) / 3 ( (2x more time spent in diastole than systole + systolic Blood pressure) divided by 3 • 2/3 time in diastole and 1/3 in systole • Ex: BP 120/80 = (120+160)/3 = 93 MAP))

Mean Arterial Pressure (MAP) formula

a. Too short of a RBC transit time due to a high cardiac output. (• mechanism of exercise-induced hypoxemia. 40% of elite endurance athletes have such high cardiac outputs that they see a drop in blood oxygen levels at high intensities (limiting their performance)this is due to a short red blood cell transit time through the LUNG (pulmonary) capillaries. Ultimately this is the limit to their performance and these athletes can NEVER exceed this ability. RBC travels too quickly past lungs to pick up sufficient oxygen (muscle can adapt but lungs cant completely) o athletes can become so fit that their VO2 (maximal oxygen uptake) max is above 70... High SV/CO (stroke volume/cardiac output) - blood goes through the lungs too quickly RBCs are not picking up enough O2 and diffusion of nutrients/O2 through capillaries is inefficient)

Mechanisms of Elite Athlete Exercise-Induced Hypoxemia? a. Too short of a RBC transit time due to a high cardiac output. b. Too many lung capillaries.

right atrium at SA node

Heart beat begins in...

venous return [veins have ONE-WAY valves] (is the rate of blood flow back to the heart through one-way valves to ensure blood goes back to heart and does NOT flow backwards. it normally limits cardiac output MUSCLE PUMP: move around-->muscle contracts, veins squeeze to send blood upwards to the heart THORACIC PUMP: breathing--> changes to blood vessels, venous return to heart)

How does blood return from the lower body to the heart?

1. NOREPINEHPRINE (direct) and EPINEPHRINE (indirect)--binding to alpha-1 receptors. 2. ANGIOTENSIN II--one millionth of a gram can increase arterial pressure by 50 mmHg. 3. ADH (VASOPRESSIN) (released in high amounts during hemorrhage where it can increase arterial pressure by 60 mmHg alone) 4. ENDOTHELIN (Extremely powerful in response to severe tissue trauma to prevent extensive bleeding.)

Humoral Factors: VASOCONSTRICTORS

a. True (• Angiogenesis: growth/development of new blood vessels ; has enzyme VEGF grows new blood vessels (can be good or bad) • Collateral Circulation: Additional blood vessels are grown as an alternate circulation path around a blocked artery or vein via another path, such as nearby minor vessels. o almost all humans over 60 have at least one small coronary vessel occluded but unnoticed because of rapid growth of collateral vessels which avoid myocardial damage 90-year old who constantly suffers from heart attacks will have more collateral blood vessels than younger people, so they are more likely to survive a heart attack o Deficiency in tissue oxygen and nutrients leads to the activation of these factors which cause destruction of the endothelial basement membrane and sprouting of new vessels via rapid reproduction of new endothelial cells that stream outward.)

Hypoxia in a muscle tissue increases HFs leading to VEGF and angiogenesis. This is a mechanism of exercise-induced cardio-protection via collateral circulation. a. True b. False

Ohm's Law (-in the COLD--body wants to send blood to most important organs, arteries CONSTRICT in fingers and nasal cavity and immune cells in nose become weaker -in HEAT (ex: steam room)---vessls DILATE to allow for diffusion and evaporation of water from skin to cool off)

Perfusion pressure = flow x resistance

b. Ca++ influx and efflux of K+ (o Pacemaker (Transmembrane) Action Potentials 2. Phase 0; Upstroke - Suprathreshold stimulus activates Na+ channels leading to rapid depolarization 3. Phase 1; Early Partial Repolarization potassium going out of cell - Efflux of K+ through channels that conduct transient outward current 4. Phase 2; Plateau: - Balance of Ca++ influx (for e-c coupling) through DHPR receptors and efflux of K+ through various K+ channels 5. Phase 3; Final Repolarization - Efflux of K+ > influx of Ca++ which rapidly increases K+ conductance and restores full repolarization 6. Phase 4; Resting Potential - Transmembrane potential determined by conductance of cell membrane to K+ ions o Non-pacemaker action potentials: calcium enters the heart for the contraction (force production in skeletal muscles) - adrenaline increases calcium permeability so heart beats stronger and faster - can become pacemakers with myocardial infarction (dead cells)

Phase 2 (plateau) of the cardiac action potential is attributed to _______. a. Ca++ Efflux and Na+ influx b. Ca++ influx and efflux of K+ c. Na+ efflux and K+ influx d. Cl- influx and Ca++ efflux

b. Atropine to reduce vagal activity (anticholinergic) (a. EDRF-->released by the endothelium to promote smooth muscle relaxation in response to rapid blood flow; b. Atropine to reduce vagal activity (anticholinergic)-->Inotropic, anticholinergic, and alkalinizing agents are used in the treatment of pulseless electrical activity (PEA). As previously stated, resuscitative pharmacology includes epinephrine and atropine. If the underlying rhythm is bradycardia (ie, heart rate < 60 bpm) associated with hypotension, then atropine should be administered. c. Vagal tone-->Activity of the vagus nerve that lowers the heart rate and decreases blood pressure (elevating levels of rest and digest activity); Increase potassium permeability - decrease resting potential; athletes haver higher vagal tone d. Acetylcholine-->SLOWS heart rate; It is parasympathetic and vagus nerve activation that releases acetylcholine onto your sinoatrial node, states Cvphysiology.com. This action decreases pacemaker rate by increasing potassium and decreasing calcium and sodium movement. As the pacemaker slows, so does your heart rate. • Inotropic Effects: increase contractility (STRENGTH) of the heart; brought on by sympathetic nervous system or anything that would cause heart to beat stronger (calcium) - Sympathetic neurons during fight or flight response releases norepinephrine; Norepinephrine increases calcium permeability in heart leading to heart to be STRONGER--> increase inotropic effect (calcium leads to increase force production is muscles) - Ex. Calcium, Catecholamines, Dopamine, Dobutamine, Dopexamine, Epinephrine (adrenaline), Isoprenaline, Norepinephrine, Angiotensin II, Eicosanoids, Prostaglandins, Phosphodiesterase, Theophylline, Glucagon, Insulin - caffeine and calcium causes inotropic event • Chronotropic Effects: something that increases the SPEED of the heart; brought on by sympathetic nervous system or anything that would cause heart to beat faster (sodium) - Sympathetic neurons also increase tachycardic responses by increasing sodium permeability in heart causing action potentials to go faster-> increase chronotropic effect - Most adrenergic agonists, Atropine, Dopamine, Epinephrine, Isoproterenol, Milrinone, Theophylline)

Produces an inotropic effect _______. a. EDRF b. Atropine to reduce vagal activity (anticholinergic) c. vagal tone d. acetylcholine

d. All of these (• Pulse Pressure: Difference between systolic and diastolic pressure o Normal: 40mmHg (b/c normal BP is 115/75 and 115-75=40) o Above average pulse pressure (60 mmHg) suggests stiff arterial vessels lack of arterial compliance o Large difference between systolic and diastolic is dangerous; linked to organ damage o Which is better 140/80 or 140/90; 140/90 b/c at least arteries are pretty compliant just need to get BP down)

Pulse pressure a. SBP-DBP b. Ideally <60 mmHg c. High PP could be linked to stiffened artery walls and organ stress d. All of these

ventricular depolarization

QRS wave

Arterial vessels (stopcocks of the circulation; conserve blood flow (ex: when cold, take blood away from extremities and pool towards organs, causing vasoconstriction)

Resistance vessels/stopcocks of the vascular system

b. Potassium d. Adenosine e. Nitric oxide f. Carbon dioxide (• Local Factor Vasodilators: Shearing stress of Q leading to Endothelial Relaxing Factor (nitric oxide or NO) which causes reduced Ca++ release in the SMC and vasorelaxation. • Adenosine (from Type II muscle fibers) and other metabolites are released in ischemic muscle and contracting muscle resulting in local vasodilation that overrides the sympathetic innervation. o NO o Hydrogen ions o Adenosine o CO2 o K+ a. Angiotensin -->VASOCONSTRICTOR c. Oxygen-->O2 is a vasoDILATOR in pulmonary arteries, and a VASOCONSTRICTOR inn systemic arteries.)

Select ALL the substances that would act as a dilator in systemic arterial blood vessels: a. Angiotensin b. Potassium c. Oxygen d. Adenosine e. Nitric oxide f. Carbon dioxide

40 (b/c normal BP is 115/75 and 115-75=40)

Normal Pulse Pressure = ______mmHg

115/75

Normal blood pressure

4900 mL/5 L per minute (• Normal reference: heart rate at rest is 70 beats per minute (60-80bpm) x average of 70 mL stroke volume (~5 L per min for stroke volume); also known as 4900 mL/5 L per minute Cardiac Output (CO) = heart rate x stroke volume)

Normal reference cardiac output

d. AV-Node (a. Atrial myocardiocyte - Cardiac muscle cells or cardiomyocytes the muscle cells (myocytes) that make up the cardiac muscle (heart muscle); In this specific case, it is the myocytes of the atrial of the heart b. Bundle branch - BUNDLE BRANCH: offshoots of the bundle of His in the heart's ventricle. They play an integral role in the electrical conduction system of the heart by transmitting cardiac action potentials from the bundle of His to the Purkinje fibers. c. Myocardiocyte bundle of HIS - The bundle of His is an important part of the electrical conduction system of the heart, as it transmits impulses from the atrioventricular node, located at the inferior end of the interatrial septum, to the ventricles of the heart. ... These fibers distribute the impulse to the ventricular muscle. d. AV-Node • Pace makers of the heart w/ Automaticity (automatically fire on own w/o any influence): i) SA node (60-80bpm); nervous system influences the average pace of 60-80 BPM, provides sinus rhythm ii) AV node (40-60 bpm); backup plan for SA node, paces heart around 40-60 bpm iii) purkinje fibers (30-50bpm))

Select the slow-response myocardial cell with automaticity. a. Atrial myocardiocyte b. Bundle branch c. Myocardiocyte bundle of HIS d. AV-Node

Rate-Induced Contractility

The faster the heart rate, the more calcium left offer between beats--allows contractions to get stronger and stronger -Ex: Premature Ventricuar contractions (PVC) are very strong because of the Treppe Phenomenon (more calcium for subsequent gradual increase in muscular contraction following rapidly repeated stimulation)

b. closure of the mitral and tricuspid valves. (• The first heart sound, or S1, forms the "lub" of "lub-dub" and is composed of components M1(mitral valve closure) and T1 (tricuspid valve closure) o It is caused by the closure of the atrioventricular valves, i.e. tricuspid and mitral (bicuspid), at the beginning of ventricular contraction, or systole. • The second heart sound, or S2, forms the "dub" of "lub-dub" and is composed of components A2 (aortic valve closure) and P2(pulmonary valve closure). o It is caused by the closure of the semilunar valves (the aortic valve and pulmonary valve) at the end of ventricular systole and the beginning of ventricular diastole.)

The first heart sound is attributed to ____________. a. Closure of the aortic and pulmonary valves b. closure of the mitral and tricuspid valves. c. Closure of the aortic and mitral valve d. Closure of the tricuspid and right av valve.

Frank-Starling Law

The greater the stretch, the stronger is the heart's contraction. This increased contractility results in an increased volume of blood ejected (Increased SV) • If heart filling (EDV) not enough, then heart would beat weak ; can cause—during diastolic heart failure (heart not filling w/ enough blood) • —getting more stretched and more aligned so stronger heartbeat; where we are at rest • —OPTIMAL force production during EXERCISE • - heart will be very weak again—cross bridges too stretched out--> Systolic heart failure: during systole or when heart contracting, not ejecting enough blood and thus hear overfills causing cross-bridges to overstretch and cause heart to get weaker • Lines represent how cross bridges look

baroreceptor reflex

The primary reflex pathway for homeostatic control of blood pressure during exercise, baroreceptors must reset acutely, causing BP rise. if BP increases too much, a dampening effect occurs and persists after excise to keep BP lowered (used for acute BP adjustments) o increases in BP at onset of exercise --> activate reflex --> may contribute to an attenuated HR response, therefore up to 40% of VO2 max increases in cardiac output are due to Stroke Volume (SV) alone -->reflex then resets

b. Closure of the Aortic and Pulmonary Valves. (• The first heart sound, or S1, forms the "lub" of "lub-dub" and is composed of components M1(mitral valve closure) and T1 (tricuspid valve closure) o It is caused by the closure of the atrioventricular valves, i.e. tricuspid and mitral (bicuspid), at the beginning of ventricular contraction, or systole. • The second heart sound, or S2, forms the "dub" of "lub-dub" and is composed of components A2 (aortic valve closure) and P2(pulmonary valve closure). o It is caused by the closure of the semilunar valves (the aortic valve and pulmonary valve) at the end of ventricular systole and the beginning of ventricular diastole.)

The second heart sound. a. Closure of the AV valves (Mitral and Tricuspid). b. Closure of the Aortic and Pulmonary Valves.

c. CO2 (• Vasodilation in terms of SYSTEMIC circulation CO2 • Vasoconstriction in terms of SYSTEMIC circulation --> ADH and CO2 o Oxygen Lack Theory: muscles surrounding arteries doesn't receive enough oxygen/nutrients lack the energy to constrict so vasodilation occurs to get more oxygen delivered High CO2 levels = dilation (in SYSTEMIC CIRCULATION) • CO2 is a vasodilator in general systemic arteries throughout the body • Needs to be more blood flow when there is a build-up of CO2 in the right leg In lungs - opposite effect, High CO2 = constriction (in PUMLONARY CIRCULATION) • Do not want to send blood flow to areas of lungs that don't not work well)

Vasodilator a. O2 b. ADH c. CO2

Ohm's Law: Perfusion pressure (is proportionate to the amount of) = flow x resistance (-in the COLD--body wants to send blood to most important organs, arteries CONSTRICT in fingers and nasal cavity and immune cells in nose become weaker -in HEAT (ex: steam room)---vessls DILATE to allow for diffusion and evaporation of water from skin to cool off)

What is Ohm's Law related to the cardiovascular system?

93 (• Mean Arterial Pressure (MAP): Average arterial pressure during one cardiac cycle o Considered a better indicator of perfusion to vital organs than systolic blood pressure o MAP = (2 x (DBP) + SBP) / 3 (2x more time spent in diastole than systole + systolic Blood pressure) divided by 3 MAP = ((2 x 75) + 130)/3 MAP =93)

What is the Mean Arterial Pressure of 130/75 blood pressure? (do not write units) __________.

Blood Pressure = Cardiac Output x peripheral resistance (o Cardiac output: heart rate x stroke volume o Peripheral resistance: the resistance of blood flow throughout the body • Measures systolic/diastolic (mmHg); first number = systolic, second = diastolic • Systolic Pressure: peak pressure exerted by blood on arterial wall - ventricular contraction (120 mmHg) o Heart contracting = 1/3 of cycle (systole) • Diastolic Pressure: lowest arterial pressure - ventricular relaxation (80mmHg) o Filling ventricles = 2/3 of cycle (diastole) • Normal - 115/75 o Elevated BP - 120 systolic while <80 diastolic o High BP stage 1 - >130 systolic or >80 diastolic, o High BP stage 2 - >140 systolic or >90 diastolic )

What is the equation for blood pressure?

100-110 BPM (o At rest, our heart is usually under 100 BPS b/c of more vagal tone o If O2 is present, the heart can beat outside of the body due to having automaticity)

What is the human intrinsic heart rate?

100-110 BPM (o At rest, our heart is usually under 100 BPS b/c of more vagal tone o If O2 is present, the heart can beat outside of the body due to having automaticity)

What is the human intrinsic heart rate?

c. Increased sodium and calcium permeability at the SA node (• Adrenergic Stimulation = Na+ and Ca+++ currents > K+ current • Vagal Stimulation = K+ current > Na+ and Ca++ currents = hyperpolarization and slowed heart rate (choice a))

Sympathetic (adrenergic) simulation of the heart causes _____. a. Increased potassium permeability at the SA node b. Increased potassium permeability at the AV node and increased sodium permeability at the SA node c. Increased sodium and calcium permeability at the SA node d. Increased sodium permeability at the SA node

a. weakened heart due to too high of an ESV and EDV (Systolic Heart failure: The heart can't pump with enough force to push enough blood into circulation. i. heart will be very weak again—cross bridges too stretched out Systolic heart failure b/c during systole or when heart contracting, not ejecting enough blood and thus heart overfills causing cross-bridges to overstretch and cause heart to get weaker Diastolic Heart failure: the lower left chamber of the heart (left ventricle) is not able to fill properly with blood during the diastolic phase, reducing the amount of blood pumped out to the body. i. If heart filling (EDV) not enough, then heart would beat weak diastolic heart failure (heart not filling w/ enough blood))

Systolic Heart Failure a. weakened heart due to too high of an ESV and EDV b. weakend heart due to insufficient EDV.

ventricular contraction (120 mmHg) (o peak pressure exerted by blood on arterial wall /Heart contracting = 1/3 of cycle (systole))

Systolic pressure represents

Chronotropic Effects

something that increases the SPEED of the heart; brought on by sympathetic nervous system or anything that would cause heart to beat faster (sodium) o Sympathetic neurons also increase tachycardic responses by increasing sodium permeability in heart causing action potentials to go faster--> increase chronotropic effect

capacitance vessels

the blood vessels that contain most of the blood and that can readily accommodate changes in the blood volume--> veins

RBC (red blood cell) transit time

time taken for an RBC to travel through a capillary -Normal time = .75 seconds -shortest time = .3 seconds -as heart rate INCREASES, ________________ DECREASES

***Diff steps of conduction pathway through heart: 1. SA Node initiates the cardiac action potential (that is why it is called a sinus rhythm. Normal is 60-80 BPM 2. Action potential spreads through atrial cells (via gap junctions containing intercalated disks [nerve fibers connecting cells]) to the AV Node 3. There is a brief AV-delay while the ventricles fill to end-diastolic volume (EDV) (~120 mL) 4. The AV node continues the action potential to the bundle of 'His' - The bundle of His is an important part of the electrical conduction system of the heart, as it transmits impulses from the atrioventricular node, located at the inferior end of the interatrial septum, to the ventricles of the heart. ... These fibers distribute the impulse to the ventricular muscle. 5. Then the action potential travels from the bundle of 'His' to right and left bundle branches w/in the ventricular septum 6. Then the action potential spreads along the purkinje fibers to complete the ventricular depolarization ( Pacing of the Heart: 1. SA node fires in the right atrium, both the right and left atria contract 2. Electric signal travels to AV node in between the right atrium and ventricle, slowing the signal briefly 3. Impulse travels to the bundle of His in between the right and left atrium, and down through the Purkinje fibers down the apex and the walls of the ventricles 4. Signal through Purkinje fibers causes the ventricles to contract and pump blood out to the body and lungs)

What is the pathway of action potential conduction along the myocardium?

1. SA NODE initiates the cardiac action potential (that is why it is called sinus rhythm. Normal 60-80BPM) 2. action potential spreads through ATRIAL CELLS (via gap functioning containing intercalated disks [nerve fibers connecting cells] to the AV NODE 3. There is a brief AV-delay while the ventricles fill to END-DIASTOLIC VOLUME (EDV= ~ 120mL) 4. the AV NODE continues the action potential to the BUNDLE OF 'HIS' 5. then the action potential travels from the BUNDLE OF 'HIS' to RIGHT and LEFT bundle branches of VENTRICULAR SEPTUM 6. then the action potential spreads along the PURKINJE FIBERS to complete VENTRICULAR DEPOLARIZATION (causing contraction)

What is the pathway of action potential conduction along the myocardium? Different steps of conduction pathway through the heart:

CAPILLARIES b/c blood flow velocity must be slow enough to allow for sufficient oxygen delivery to the tissues (o Ex: Exercise training increases cardiac output (larger heart and more stroke volume). This would decrease red blood cell transit time and affect oxygen delivery. Fortunately, muscle tissue will increase capillary density proportional to increases in cardiac output. o Ex 2: EXCEPTION; mechanism of exercise-induced hypoxemia. 40% of elite endurance athletes have such high cardiac outputs that they see a drop in blood oxygen levels at high intensities (limiting their performance)-->this is due to a short red blood cell transit time through the LUNG (pulmonary) capillaries. Ultimately this is the limit to their performance and these athletes can NEVER exceed this ability. RBC travels too quickly past lungs to pick up sufficient oxygen (muscle can adapt but lungs cant completely)

Where is blood flow velocity the slowest and why?

veins (Capacitance vessels: the blood vessels that contain most of the blood and that can readily accommodate changes in the blood volume)

Which are the capacitance vessels?

b. Inotropic Effect (• Chronotropic Effect: something that increases the SPEED of the heart o brought on by sympathetic nervous system or anything that would cause heart to beat faster (sodium) • Inotropic Effect: increases CONTRACTILITY (STRENGTH) of heart o Sympathetic neurons during fight or flight response releases norepinephrine; Norepinephrine increases calcium permeability in heart leading to heart to be STRONGER--> increase inotropic effect o Caffeine and calcium causes inotropic effect)

Which of the following leads to the increase contractility of the heart? a. Chronotropic effect b. Inotropic Effect

a. CO2 is a vasoconstrictor in pulmonary arteries, but not systemic arteries (• CO2 is VASOCONSTRICTOR pulmonary arteries (b/c CO2 is indicator that not enough oxygen being produced) • ***why would a COPD or a smoking patient be susceptible to right side heart failure? o b/c CO2 in lungs causes right side of heart to work that much harder to get vasoconstricted lungs o for smokers, right side of heart always under stress b/c right side of heart is working so hard to get blood flow through vasoconstricted arteries)

Why would the right ventricle be under stress in a patient with lung disease? a. CO2 is a vasoconstrictor in pulmonary arteries, but not systemic arteries b. O2 is a vasoconstrictor in pulmonary arteries, but not systemic arteries.

systemic

_________________ arteries: o CO2 = VasoDILATOR o O2 = vasoCONSTRICTOR

pulmonary

__________________ arteries: o CO2 = VasoCONSTRICTOR o O2 = vasoDILATOR

central controls

______________________ of Cardiorespiratory responses to Exercise: -motor cortex, cerebellum sends signals down to motor units and recruitment--> on way down, passes brain stem-->through brain stem signals cardiorespiratory control centers in medulla oblongata to SPEED UP HEART RATE AND INCREASE VO2 in response to exercise

peripheral controls

_______________________ of Cardiorespiratory responses to Exercise: increased temperature, tension, and local factors send sensory information to the spinal cord-->from the spinal cord to the brain stem: cardiorespiratory control centers are signaled to ACTIVATE MOTOR UNIT ACTION AND CONSTRUCT BLOOD FLOW FROM ORGANS that are UNNECESSARY during exercise/muscle contraction

a) 60 b) shock (o Types of shock (drop in BP - pass out, potential nervous damage from lack of O2 to brain) Cardiogenic Anaphylactic - allergy gets into blood vessels and histamine causes vessels to dilate in response Septic - response to infection in blood stream Insulin Psychogenic - panic causes vessels to dilate)

___a____ mmHG of arterial pressure is required for perfusion of the brain to sustain blood flow to main arterial organs (anything lower can result in ___b___)

Right Ventricular Hypertrophy

a form of ventricular hypertrophy affecting the right ventricle. ... If conditions occur which decrease pulmonary circulation, meaning blood does not flow well from the heart to the lungs, extra stress can be placed on the right ventricle. a lung disease patient with COPD (Cardiopulmonary Disease) be at risk for ___________________________________ because the ventricle has to work harder to overcome the high pressure to get blood flow through vasoconstricted arteries, making it larger

Ejection Fraction

a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction stroke volume (70 mL)/end diastolic volume (120 mL) -->70 mL/120 mL = 59% • If low (around 30%) - indication of heart failure

retrolental fibroblasia

abnormal proliferation of fibrous tissue immediately behind the lens of the eye (due to angiogenesis which is the growth/development of new blood vessels), leading to blindness. It affected many premature babies in the 1950s, owing to the excessive administration of oxygen. • (pre-mature infants put in high oxygen environment tanks and when taken out of this environment would cause eyes to grow abundance of blood vessels leading to blindness (high oxygen environment--> low oxygen environment NOT good thus leading to blindness)

vagal tone

activity of the vagus nerve that lowers the heart rate and decreases blood pressure (elevating levels of rest and digest activity); increases potassium permeability-- decreases resting potential EXERCISE-INDUCED BRADYCARDIA: endurance athletes have higher vagal tone and sinus bradycardia (usually a sign of fitness and nothing serious)

End Systolic Volume (ESV)

amount of blood that comes out of every heart beat - Normal Resting Stroke Volume = 70 mL

End Diastolic Volume (EDV)

volume in average ventricle at end of filling (120 mL) - PRELOAD

End Diastolic Volume (EDV)

volume in average ventricle at end of filling (120 mL) - PRELOAD o One of most important things in determining if someone has heart failure

Bainbridge reflex

an increase in heart rate due to an increase in central venous pressure o a stretch of the heart causes a release of atrial natriuretic factor (ANF -> a strong diuretic causing the kidneys to excrete water and sodium) which decreases ADH to increase urine output and vasodilation (your body believes it has too much blood volume so it produces a diuretic effect) o causes you to get rid of water to reverse excessive volume loading, o causes increased HR to get rid of extra fluid

End Diastolic Volume (EDV)

volume in average ventricle at the end of filling (120mL--preload)

Stroke Volume (SV)

volume of the heart after contraction (50mL)

stroke volume (SV)

volume of the heart after contraction (70 mL)

Afterload

arterial pressure outside ventricle, pressure against which heart works to eject blood

70 mL stroke volume (~5 L per min for stroke volume)

average stroke volume

heart -->aorta-->large arteries-->small arteries -->arterioles-->capillaries (where gas exchange occurs); from capillaries -->venules (blue colored) -->small veins-->large veins --> vena cava

way blood flows through body

venous capacitance

can hold up to 70% of blood volume o Veins (deoxygenated blood into the heart) have a little muscle but very stretchy 2/3rds of blood on venous side of body; Blood gets from legs to heart by one-way valves that prevent backflow Blood through capillaries move at slow velocityVENUS RETURN: Venous return is the rate of blood flow back to the heart. It normally limits cardiac output. • 1. Muscle Pump: muscles contracting from a little movement massages veins to squeeze blood up back to the heart (one-way valves to prevent blood from seeping back down) Varicose Veins: veins with damaged valves Staying still after exercise -> poor venous return • 2. Thoracic Pump: every time you take a breath in, that breath in expands your blood vessels; creates changes in thoracic pressure to draw blood up through heart like straw o Veins have one-way valve

ventricular relaxation (80mmHg) (o lowest arterial pressure Filling ventricles = 2/3 of cycle (diastole))

diastolic pressure represents

Exercise-induced bradycardia

endurance athletes have higher vagal tone (lowers heart rate and decreases BP) and sinus bradycardia (usually a sign of fitness and nothing serious)

preload

filling of the ventricle prior to contraction; _______ needs to EXCEED the afterload to have a healthy/adequate stroke volume and ejection fraction to prevent heart failure (EDV)

angiogenesis

growth/development of new blood vessels ; has enzyme VEGF--> grows new blood vessels (can be good or bad) o Good: Trained muscle will have more blood vessels delivering more fat and sugar to muscles to burn it up Collateral vessels in the heart: how exercise protects us from heart attacks by growing more vessels around myocardium to get more blood vessels to heart muscle o Bad: types of blindness in eye (ex: increase development of blood vessels in eye b/c not getting enough oxygen there)--> RETROLENTAL FIBROLASIA Diabetes is number 1 reason for blindness Macular degeneration that could lead to blindness Cancer cells grow when develop more blood vessels causing them to become more harmful (one cause of growing more blood vessels is INFLAMMATION) diet high in plants helps in preventing cancer cells from developing blood vessels Some cancer drugs called antigenic drugs Obesity: fat cells need blood vessels to grow which causes them to form o Angiogenesis not good nor bad Placenta Scar tissue

stroke volume

how much blood comes out of your heart with every beat (average of 70 mL per every beat or ~5L per min for stoke volume)

Inotropic Effects

increase contractility (STRENGTH) of the heart; brought on by sympathetic nervous system or anything that would cause heart to beat stronger (calcium) o Sympathetic neurons during fight or flight response releases norepinephrine; Norepinephrine increases calcium permeability in heart leading to heart to be STRONGER increase inotropic effect (calcium leads to increase force production is muscles) -------caffeine and calcium causes inotropic event

Endothelium-Derived Relaxing Factor (EDRF)

is produced and released by the endothelium to promote smooth muscle relaxation in response to rapid blood flow (viscous drag and shear stress along endothelial walls) _______________ Nitric Oxide Synthase

vasodilator theory

muscle tissues release various chemicals that dilate arteries such as adenosine, CO2, histamine, K+, H+ or lactate -greater metabolic rate or lower O2 available = greater release of vasodilator substances Exercise releases vasodilators -> muscle pump - increased blood flow to working area with low O2

oxygen-lack theory

muscles surrounding arteries don't receive enough oxygen/nutrients, thus lacking the energy to constrict so VASODILATION OCCURS to get MORE OXYGEN delivered -High CO2 levels = vasodilation (in systemic circulation) -in lungs, opposite effect. High CO2 = vasoconstriction (in pulmonary circulation)

70 beats per minute (60-80bpm)

normal heart rate at rest

1. BRADYKININ (Inflamed tissues release bradykinin which lead to powerful arteriolar vasodilation and increased capillary permeability) 2. HISTAMINE (released by virtually all tissues by mast cells of damaged tissues or basophils in the blood; especially prominent during allergic reactions)

o Humoral Factors: VASODILATORS

58% (stroke volume (70 mL) / end diastolic volume (120 mL) = 58%)

o In normal individual ejection fraction is...

ejection fraction

o In normal individual: stroke volume (70 mL) / end diastolic volume (120 mL) = 58% Stroke Volume: how much blood comes out of your heart with every beat (average of 70 mL per every beat or ~5L per min for stoke volume) End Diastolic Volume (EDV): volume in average ventricle at end of filling (120 mL) - PRELOAD o One of most important things in determining if someone has heart failure

PVC (Premature Ventricular Contraction)

one of the most common arrhythmias (irregular heart beat); irritable cells contract prematurely before calcium left over from previous heart beat/contraction- feels like a palpitation

SA --> AV --> Bundle of HIS --> L and R bundle branches --> purkinje fibers (SA Node initiates the cardiac action potential (that is why it is called a sinus rhythm. Normal is 60-80 BPM Action potential spreads through atrial cells (via gap junctions containing intercalated disks [nerve fibers connecting cells]) to the AV Node There is a brief AV-delay while the ventricles fill to EDV (~120 mL) The AV node continues the action potential to the bundle of 'His' Then the action potential travels from the bundle of 'His' to right and left bundle branches w/in the ventricular septum Then the action potential spreads along the purkinje fibers to complete the ventricular depolarization)

pathway of pacemaker

Posillues' Law

resistance through blood vessel is proportional to the pressure difference on both ends of tubes--thus resistance is INVERSELY proportional to radius to the 4th power -dilating a vessel to 2x the size= reduce resistant by 1600% -arterial vessels constrict and dilate so blood flow and pressure are greatly influenced)

arterial vessels [stopcocks of the circulation; conserve blood flow (ex: when cold, take blood away from extremities and pool towards organs, causing vasoconstriction)]

resistance vessels or stopcocks of the vascular system

Pacemakers

slow response action potentials and automaticity 1. SA node (60-80bpm); nervous system influences the average pace of 60-80 BPM, provides sinus rhythm 2. AV node (40-60 bpm); back up plan for SA node, paces heart around 40-60 bpm 3. purkinje fibers (30-50bpm)

-BP medication and diuretics lessen the load on the heart by reducing the volume and allowing blood to be pumped out -vasodilator would reduce the AFTER-load pressure outside of the heart (Systolic heart failure: during systole or when heart contracting, not ejecting enough blood and thus hear overfills causing cross-bridges to overstretch and cause heart to get weaker)

• Based on Frank-Starling's Law, how could a diuretic and vasodilator be administered to help someone in systolic heart failure.

Frank-Starling Law (length tension relationship): end diastolic volume (EV) is directly related to the contractile strength of the ventricles and stroke volume (SV). the more ventricular filling, the greater the stretch, the stronger the muscles o Effects at rest: The less ventricular filling, the less stretch ;the relaxed sarcomere length of cardiac muscle cells, in a resting ventricle, is lower than the optimal length for contraction. o Effects at maximal exercise: Augmentation of LV-EDV (LEFT VENTRICLE and END DIASTOLIC PRESSURE) with training; optimal capacity of blood b/c exercise increases athlete's elasticity of heart (why athletes have higher SV) Exercise increases the compliance of the heart wall to allow for greater expansion Exercise induced increases in plasma volume may be the mechanism of increased diastolic filling time during exercise SYSTOLE Exercise causes a 0-25% increase in ventricular mass without increases in sarcomere number. Ventricular mass increases in longitudinal and cross-sectional dimensions. A longitudinal increase in ventricular mass by 5% elicits and a 16% increase in chamber size. o Effects in the case of systolic factor: Systolic Heart Failure: preload cannot overcome after load (pressure in aorta), higher than normal EDV; however if the heart overloads and becomes too stretched, it gets weaker. • Heart 'floods', blood backs up into lungs -> congestive heart failure and edema • Use BP medications and diuretics to lessen the load on the heart • Ex. significant hypertension

• Have a firm grasp of the Frank-Starling Law of the heart. Know it's effects at rest, maximal exercise, and in the case of systolic heart failure.

o Pacemaker (Transmembrane) Action Potentials: slow response action potentials and automaticity 1. Phase 0; Upstroke - Suprathreshold stimulus activates Na+ channels leading to rapid depolarization 2. Phase 1; Early Partial Repolarization potassium going out of cell - Efflux of K+ through channels that conduct transient outward current 3. Phase 2; Plateau: - Balance of Ca++ influx (for e-c coupling) through DHPR receptors and efflux of K+ through various K+ channels 4. Phase 3; Final Repolarization - Efflux of K+ > influx of Ca++ which rapidly increases K+ conductance and restores full repolarization 5. Phase 4; Resting Potential - Transmembrane potential determined by conductance of cell membrane to K+ ions ----------------------------------------------- o Non-pacemaker action potentials: Fast response action potentials o calcium enters the heart for the contraction (force production in skeletal muscles) - adrenaline increases calcium permeability so heart beats stronger and faster - can become pacemakers with myocardial infarction (dead cells)

• How action potentials differ in pace makers v. non-pacemakers:

ATROPINE increases adrenaline of the heart--acetylcholine, norepinephrine and epinephrine in heart completely block vagus nerve and block PNS - SNS would be the inotrope that increases stroke volume at any EDV (• Inotropic Drug: drug or hormone causes heart to be stronger, increases heart permeability to calcium (calcium increases force production in muscles) • End Diastolic Volume (EDV): volume in average ventricle at end of filling (120 mL) - PRELOAD • Stroke Volume (SV): volume of the heart after contraction (50 mL))

• How would an inotropic drug, like Atropine (anticholinergic drug) augment SV at a given EDV?

• BP with 2 liters of blood loss -> baroreceptor kicks in, heart is accelerated, pressure increases/regulates Blood can get to brain and heart - negative feedback mechanism successful • BP with 3 liters of blood loss -> blood pressure goes down but even with baroreceptors, not enough blood flow to coronary arteries—POSITIVE FEEDBACK - Organs DO NOT get enough energy and oxygen CRITICAL (usually leads to death)

• Using negative, versus positive feedback, differentiate between two and three liters of blood loss on the acute mortality risk.

(Electrocardiogram (EKG): studies electric charges throughout the heart for every beat through the change in electric potential as sodium and calcium ions flow through the heart, and potassium ions out of the heart) -Heart beat begins in right atrium at SA node P Wave = Atrial depolarization in response to SA node triggering (sodium has gone in followed by calcium and pumps blood to ventricles) PR interval: AV delay to allow ventricular chambers to fill up w/ blood; follow atrial depolarization to ventricular contraction. signal enters ventricle via AV node QRS Wave = ventricular depolarization (triggers main pumping contractions) ST segment= beginning of ventricular repolarization, should be flat (very sensitive to oxygen levels in heart and if elevated, sign of someone having a heart attack) T Wave= ventricular repolarization (potassium comes back out of heart through cell membranes), heart ventricles are relaxing

■ Be able to define the key segments of the electrocardiogram.

REACTIVE HYPEREMIA: occluded blood flow increases 4-7 fold when opened long enough to "pay back" the exact O2 deficit during occlusion (metabolic blood flow regulation)--> lack of oxygen causes an immediate payback of blood flow (think of rubber band around finger) occlusion--> removal-->dramatic increase in blood flow ---------------------------------------------------- ACTIVE HYPEREMIA: up to 20 fold increase during muscle contraction (EXERCISE) releasing large quantities of vasodilator substances-->metabolically active muscle tissues cause blood vessels to dilate o Arteries over-dilate during exercise -> constrict as a response (burning sensation) -> less oxygen to muscles results in switch anaerobic metabolism -> production of lactate (• Oxygen-Lack Theory: muscles surrounding arteries doesn't receive enough oxygen/nutrients --> lack the energy to constrict so vasodilation occurs to get more oxygen delivered)

■ Understand Reactive Hyperemia and Active Hyperemia. • (part of ACUTE CONTROL of the oxygen -lack theory)

(5) 1. NO (nitric oxide released leading to endothelial relaxing factor causing reduction in Ca++ release in the SMC and vasorelaxation) 2. Adenosine (from Type II muscle fibers and other metabolites are released in ischemic muscle and contracting muscle resulting in local vasodilation that overrides the sympathetic innervation.) 3. Hydrogen ions 4. CO2 5. K+

■ What are some potent, local, vasodilators?

• Beri Beri (" I cannot, I cannot"): Inflammation of nerves, heart failure and weakening of capillary walls due to a lack of B vitamins (Lack of thiamin (B1) and Niacin and Riboflavin lead to 2-3 fold increase in blood flow). o These B vitamins are required for energy/ oxidative phosphorylation (Smooth muscle cells of arteries cannot constrict/dilate) o Lack of nutrients -> inability of smooth muscles to contract and induce venous return -> cannot get blood to brain standing up (b/c blood stays pooled in legs), cannot redirect oxygen/nutrients to muscles -> dizzy, immobile Explains OXYGEN-LACK THEORY

■ What is Beri Beri?

40% of elite endurance athletes have such high cardiac outputs that they see a drop in blood oxygen levels at high intensities (limiting their performance)-->this is due to a short red blood cell transit time through the LUNG (pulmonary) capillaries. -Ultimately this is the limit to their performance and these athletes can NEVER exceed this ability. -RBC travels too quickly past lungs to pick up sufficient oxygen (muscle can adapt but lungs cant completely)

■ What is Exercise Induced Hypoxemia

Premature Ventricular Contraction (PVC): Two-early heartbeat that originates in the ventricles and disrupts the heart's normal rhythm; irritable cells contract prematurely before calcium left over from previous heart beat/contraction- feels like a palpitation -The pattern is a normal beat, an extra beat (the PVC), a slight pause, then a stronger-than-normal beat. -->This pattern may occur randomly or at definite intervals (most common cause of irregular heart beats) -The heart fills with more blood during the pause following the PVC, giving the next BEAT EXTRA FORCE--> PVCs are very strong contractions because of the TREPPE PHENOMEMON (more calcium for subsequent contraction).

■ What is a PVC?

Additional blood vessels are grown as an alternate circulation path around a blocked artery or vein via another path, such as nearby minor vessels. o almost all humans over 60 have at least one small coronary vessel occluded but unnoticed because of rapid growth of collateral vessels which avoid myocardial damage

■ What is collateral circulation?

Rate-Induced Contractility: the faster the heart rate, the more calcium left offer between beats--allows contractions to get stronger and stronger -Ex: Papillar Muscle Contractions are very strong because of the Treppe Phenomenon (more calcium for subsequent gradual increase in muscular contraction following rapidly repeated stimulation)

■ What is meant by Rate-Induced Contractility?

"AUTOREGULATION of BLOOD FLOW"--when arterial pressure changes from normal (it is not proportional) -MYOGENIC (MUSCLE_RELATED) THEORY: Sudden stretch of vessel lumen increasesCa++ permeability to cause contraction/vasoconstriction LOW level of stretch reduces Ca++ influx to cause relaxationbrings down blood flow **metabolic factors OVERRIDE myogenic

■ What is the Myogeneic Theory of Autoregulation?

sinus arrhythmia: An irregular heartbeat that's either too fast or too slow o Ex: Respiratory sinus arrhythmia—heartbeat changes pace during inhale and exhale Heartbeat cycles w/ breath in—breathe in, HR increases o The "sinus" refers to the natural pacemaker of the heart which is called the sinoatrial (or sinus) node (SA NODE). o Athletes have sinus bradycardia because their larger left ventricle takes longer to fill up, making the SA node pace the HR lower than normal; still this is normal rhythm

■ What is the sinus arrhythmia?

(Transformation of Non-Pacemaker Cells into Pace Maker) Ischemic heart disease and myocardial infarction -ISCHEMIC HEART DISEASE: can become pacemakers if heart isnt getting enough oxygen (ischemia), it doesnt have enough energy (ATP) to pump in sodium -MYOCARDIAL INFARCTION (heart attack): a blockage of blood flow to the heart muscle o can become pacemakers with myocardial infarction (dead cells)

■ When can non-pacemaker cells become pace maker cells?

PACEMAKERS of the heart w/ automaticity: 1. SA node (60-80bpm); nervous system influences the average pace of 60-80 BPM, provides sinus rhythm 2. AV node (40-60 bpm); back up plan for SA node, paces heart around 40-60 bpm 3. purkinje fibers (30-50bpm) NON-pacemakers: Ventricular cells o Non-pacemaker action potentials: Fast response action potentials ----------------- PACEMAKERS of the heart w/ automaticity: 1. SA node (60-80bpm); nervous system influences the average pace of 60-80 BPM, provides sinus rhythm 2. AV node (40-60 bpm); back up plan for SA node, paces heart around 40-60 bpm 3. purkinje fibers (30-50bpm) (all 3 have a higher resting membrane close to threshold; easier to depolarize Depolarization; loss of the difference in charge between the inside and outside of the plasma membrane of a muscle or nerve cell due to a change in permeability and migration of sodium ions to the interior sinoatrial (SA) node on the wall of the right atrium initiates depolarization in the right and left atria, causing contraction, which is symbolized by the P wave on an electrocardiogram o Pacemaker (Transmembrane) Action Potentials 1. Phase 0; Upstroke - Suprathreshold stimulus activates Na+ channels leading to rapid depolarization 2. Phase 1; Early Partial Repolarization potassium going out of cell - Efflux of K+ through channels that conduct transient outward current 3. Phase 2; Plateau: - Balance of Ca++ influx (for e-c coupling) through DHPR receptors and efflux of K+ through various K+ channels 4. Phase 3; Final Repolarization - Efflux of K+ > influx of Ca++ which rapidly increases K+ conductance and restores full repolarization 5. Phase 4; Resting Potential - Transmembrane potential determined by conductance of cell membrane to K+ ions slow response action potentials and automaticity w/ pacemakers ---------------------------------- • NON-pacemakers: Ventricular cells o Non-pacemaker action potentials: Fast response action potentials calcium enters the heart for the contraction (force production in skeletal muscles) - adrenaline increases calcium permeability so heart beats stronger and faster - can become pacemakers with myocardial infarction (dead cells)

■ Which myocardial cells are pace makers, and how do the action potentials differ in those cells from non-pacemakers?

(Cardiopulmonary Disease (COPD): a problem getting air out of lungs, air trapped trying to escape) -COPD patients' pulmonary arteries are constricted b/c there is more CO2 in the lungs than O2 causing BP to increase--> this ultimately leads to RIGHT VENTRICULAR HYPERTROPHY b/c the ventricle has to work harder to overcome the high pressure to get blood flow through vasoconstricted arteries causing the right ventricle to be larger

■ Why would a lung disease patient with COPD be at risk for right ventricular hypertrophy?

HYPERVENTILATION causes CO2 (dilator) to decrease leading to increase in O2 causing arteries in brain to constrict and thus bleeding will decrease as a result (• Specific acute control of blood flow: o If someone has brain arterial bleeding, you DON'T put pressure on it b/c causes brain damage such as subdermal hematoma (whereas any other arterial bleed you would apply direct pressure).... INSTEAD, hyperventilate the patient (causing them to breath faster) and thus causing bleeding to slow down this is due to when breath off CO2 less CO2 in blood causes arteries to constrict (b/c CO2 is a vasodilator in systemic circualtion) and lower blood flow)

■ Why would hyperventilation of a patient help reduce cerebral hemorrhage?

cardiac cycle: the period of time that begins with the contraction of the atria and ends with ventricular relaxation (comprises all the physiological events associated w/ a single heart beat including electrical events, mechanical events [pressures and volumes] and heart sounds -o The cardiac cycle is essentially split into two phases, systole (the contraction phase) and diastole (the relaxation phase). Each of these is then further divided into an atrial and ventricular component. The cardiac cycle therefore proceeds in four stages: 1.Atrial systole: lasts about 0.1 seconds - both atria contract and force the blood from the atria into the ventricles. 2.Ventricular systole: lasts about 0.3 seconds - both ventricles contract, blood is forced to the lungs via the pulmonary trunk, and the rest of the body via the aorta. 3.Atrial diastole: lasting about 0.7 seconds - relaxation of the atria, during which the atria fill with blood from the large veins (the vena cavae). 4.Ventricular diastole: lasts about 0.5 seconds - begins before atrial systole, allowing the ventricles to fill passively with blood from the atria. • Heart Sounds 1. Lub: mitral and tricuspid valve closing (systole)-->S1 2. Dub: aortic and pulmonary valve closing (diastole)-->S2 • Aortic Pressure: Central aortic blood pressure is the blood pressure at the root of aorta. • Atrial Pressure: measure of blood pressure w/in atrium of heart • Ventricular Pressure: measure of blood pressure w/in ventricles of heart ---------------------- • Electrocardiogram (EKG): studies electric charges throughout the heart for every beat through the change in electric potential as sodium and calcium ions flow through the heart, and potassium ions out of the heart o P Wave: Represents atrial depolarization in atrium (sodium has gone in followed by calcium), SA node fires Electrical signal spreads across cells of the right and left atria when heart is full - pumps blood through to the ventricles o QRS Wave: up...down..up--> represents ventricular depolarization in ventricles, triggers main pumping contractions Sodium and calcium moving from top to inside of the heart. Hidden within QRS complex is the atrial repolarization (unseen in an EKG and thus NO wave of atrial repolarization) QRS complex would be farther apart for an athlete (slower heart rates) o T Wave: Ventricular repolarization (potassium comes back out of heart through cell membranes), heart ventricles are relaxing, charge is resting positive inflection, potassium coming back out of ventricles ventricular repolarization o S-T segment: very sensitive to oxygen levels in the heart; if line is elevated, that is a sign of someone having a heart attack Depressed S-T segment, common sign that heart not getting enough oxygen o PR interval shows us if we have heart blockage; AV DELAY to allow ventricular chambers to fill up w/ blood

■ Be able to describe the events of the cardiac cycle, including the aortic pressure, atrial pressure, ventricular pressure, EKG, and heart sounds, from Ventricular Depolarization to Atrial Systole.

OXYGEN-LACK THEORY: muscles surrounding arteries don't receive enough oxygen/nutrients, thus lacking the energy to constrict so VASODILATION OCCURS to get MORE OXYGEN delivered -High CO2 levels = vasodilation (in systemic circulation) -in lungs, opposite effect. High CO2 = vasoconstriction (in pulmonary circulation) ------------------------------------------------ VASODILATOR THEORY: muscle tissues release various chemicals that dilate arteries such as adenosine, CO2, histamine, K+, H+ or lactate -greater metabolic rate or lower O2 available = greater release of vasodilator substances Exercise releases vasodilators -> muscle pump - increased blood flow to working area with low O2

■ Be able to differentiate between the Oxygen-Lack Theory, and the Vasodilator Theory of acute blood flow regulation.

BARORECEPTOR REFLEX-->DECREASES HR; The primary reflex pathway for homeostatic control of blood pressure; feedback mechanisms will alter the HR and blood vessel dilation to maintain blood pressure at appropriate levels -during exercise, baroreceptors must reset acutely, causing BP rise. if BP increases too much, a dampening effect occurs and persists after excise to keep BP lowered (used for acute BP adjustments) o increases in BP at onset of exercise --> activate reflex --> may contribute to an attenuated HR response, therefore up to 40% of VO2 max increases in cardiac output are due to Stroke Volume (SV) alone -->reflex then resets (feedback mechanisms will alter the HR and blood vessel dilation to maintain blood pressure at appropriate levels - transmit ion of nerve impulses fr baroreceptors to medulla in response to change in blood pressure - increases PSNS, decreases sympathetic nervous system) ---------------------------------------------------- BAINBRIDGE REFLEX-->INCREASES HR; INCREASES HR; increased blood volume accelerates HR at slow HR o a stretch of the heart causes a release of ATRIAL NATRURETIC factor (ANF) [a strong diuretic causing the kidneys to excrete water and sodium which decreases ADH to increase urine output and vasodilation (your body believes it has too much blood volume so it produces a diuretic effect) o causes you to get rid of water to reverse excessive volume loading, o causes increased HR to get rid of extra fluid

■ Be able to explain the Baroreceptor Reflex and the Bainbridge Reflex

• Oxygen plays a role in angiogenesis (growth/development of new blood vessels ; has enzyme VEGF--> grows new blood vessels (can be good or bad); e.g. retrolental fibroblasia: Retrolental Fibroblasia: abnormal proliferation of fibrous tissue immediately behind the lens of the eye (due to angiogenesis which is the growth/development of new blood vessels), leading to blindness. It affected many premature babies in the 1950s, owing to the excessive administration of oxygen. • (pre-mature infants put in high oxygen environment tanks and when taken out of this environment would cause eyes to grow abundance of blood vessels leading to blindness (high oxygen environment--> low oxygen environment NOT good thus leading to blindness)

■ Explain retrolental fibroblasia

Systemic arteries: o CO2 = VasoDILATOR o O2 = vasoCONSTRICTOR --------------------------------------- Pulmonary arteries: o CO2 = VasoCONSTRICTOR o O2 = vasoDILATOR

■ How is vasodilation / vasoconstriction different in the pulmonary vessels versus the systemic?

o Humoral Factors: VASOCONSTRICTORS 1. NOREPINEHPRINE (direct) and EPINEPHRINE (indirect) 2. ANGIOTENSIN II 3. ADH (VASOPRESSIN) (released in high amounts during hemorrhage where it can increase arterial pressure by 60 mmHg alone) 4. ENDOTHELIN (Extremely powerful in response to severe tissue trauma to prevent extensive bleeding.) ----------------------------------------------- o Humoral Factors: VASODILATORS 1. BRADYKININ (Inflamed tissues release bradykinin which lead to powerful arteriolar vasodilation and increased capillary permeability) 2. HISTAMINE (released by virtually all tissues by mast cells of damaged tissues or basophils in the blood; especially prominent during allergic reactions)

■ Know humoral vasoconstrictors and dilators.

Angiogenic Factors: VEFG, fibroblast, growth factor, angiogenin DEFICIENCY in TISSUE OXYGEN and nutrients (hypoxia induced factors) can lead to the activation of angiogenic factors which cause DESTRUCTION of the endothelial basement membrane and SPROUTING new vessels via rapid reproduction of new endothelial cells that stream outward • Vascularity determined by maximum flow need, NOT average need.

■ Know the mechanism that hypoxia-induced factors can use to promote the expression of angiogenic factors.

PERIPHERAL CONTROLS of Cardiorespiratory responses to Exercise: increased temperature, tension, and local factors send sensory information to the spinal cord-->from the spinal cord to the brain stem: cardiorespiratory control centers are signaled to ACTIVATE MOTOR UNIT ACTION AND CONSTRUCT BLOOD FLOW FROM ORGANS that are UNNECESSARY during exercise/muscle contraction ---------------------------------------------------- CENTRAL CONTROLS of Cardiorespiratory responses to Exercise: -motor cortex, cerebellum sends signals down to motor units and recruitment--> on way down, passes brain stem-->through brain stem signals cardiorespiratory control centers in medulla oblongata to SPEED UP HEART RATE AND INCREASE VO2 in response to exercise

■ Know, both, peripheral and central controls of cardiorespiratory responses to exercise.